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Modulation of bone turnover by Cissus quadrangularis after ovariectomy in rats

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Abstract

In women, age-related bone loss is associated with increased risk of bone fracture. Existing therapies are associated with severe side effects; thus, there is a need to find alternative medicines with less or optimal side effects. Cissus quadrangularis (CQ), an Ayurvedic medicine used to enhance fracture healing, was tested for its bone protective properties and studied to discern the mechanism by which it is beneficial to bone. Female Sprague Dawley rats were either sham operated or ovariectomized and were fed CQ for 3 months. Several biochemical markers, cytokines and hormones were assayed. Femur, tibia and lumbar vertebrae were subjected to pQCT and µCT densitometry. MC3T3 cells were cultured, treated with CQ and used to analyze miRNA content and subjected to qPCR for gene expression analysis related to bone metabolism. CQO rats showed protected bone mass and microarchitecture of trabecular bone in the distal femoral metaphysis and the proximal tibial metaphysis. The lumbar vertebrae, however, showed no significant changes. Serum protein expression levels of P1NP increased and Trap5b and CTX levels decreased with in vivo CQ treatment. Some influence on the anti- and pro-inflammatory markers was also observed. Significantly high level of estradiol in the CQO rats was observed. In vitro expression of a few genes related to bone metabolism showed that osteocalcin increased significantly. The other genes—collagen I expression, SPP1, BMP2, DCAT1—decreased significantly. Certain miRNA that regulate bone turnover using the BMP pathway and Wnt signaling pathways were upregulated by CQ. qPCR after acute treatment with CQ showed significantly increased levels of osteocalcin and decreased levels of Wnt/β catenin antagonist DCAT1. Overall, CQ protected the microarchitecture of the long bones from ovariectomy-induced bone loss. This may be because of decreased inflammation and modulation through the BMP and Wnt signaling pathways. We conclude that CQ is a potential therapeutic agent to treat postmenopausal osteoporosis with no side effects.

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Acknowledgements

We acknowledge Ms. Erika Varela, Mr. Eberto Presas for helping with the surgeries, feeding and weighing the rats regularly and Mr. Ali N Bahadur for doing some of the μCT scanning. This research did not receive any specific grant from funding agencies in the public, commercial, or non-profit sectors.

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Authors and Affiliations

  1. Department of Health and Biomedical Sciences, University of Texas Rio Grande Valley, 1201, W University Dr., Edinburg, TX, 78539, USA

    Juan M. Guerra, Ednia Gutierrez, Saraswathy Nair & Jameela Banu

  2. Department of Biology, University of Texas Rio Grande Valley, 1201, W University Dr., Edinburg, TX, 78539, USA

    Juan M. Guerra & Jameela Banu

  3. Department of Lab Animal Resources, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229, USA

    Martha A. Hanes

  4. Department of Lab Animal Resources, University of Texas Rio Grande Valley, 1201, W University Dr, Edinburg, TX 78539, USA

    Cordelia Rasa

  5. Poorveegam Research Trust, Pondicherry, India

    Nagarajan Loganathan

  6. School of Medicine, University of Texas Rio Grande Valley, 1201 W University Dr, Edinburg, TX, 78539, USA

    Wendy Innis-Whitehouse

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  1. Juan M. Guerra
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Correspondence to Jameela Banu.

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Guerra, J.M., Hanes, M.A., Rasa, C. et al. Modulation of bone turnover by Cissus quadrangularis after ovariectomy in rats. J Bone Miner Metab 37, 780–795 (2019). https://doi.org/10.1007/s00774-018-0983-3

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